Our long term goal is to determine the molecular basis for specific interneuronal recognition. Our working hypothesis is that this is mediated by interaction of a specific protein on one cell with a specific carbohydrate receptor on another cell. Many of the proposed studies will be made with cellular slime molds since they may prove a convenient model system for studying cell recognition like that which might be employed in the nervous system. Other studies will be made with embryonic chick brain. 1. Slime molds. We have found that two species of cellular slime molds, D. discoideum and P. pallidum, show extensive synthesis of carbohydrate binding proteins as the cells differentiate from a unicellular form to a form in which they become cohesive in a species-specific manner. The proteins are discriminable by physical-chemical properties and by carbohydrate binding specificity. They are found on the cell surface; and our working hypothesis is that they are responsible for species-specific cell association by binding with specific carbohydrate receptors that are unique to each species. In the proposed work we will determine: a) generality of this finding with other species of slime molds; b) sugar specificity of the carbohydrate binding proteins from other species; c) surface distribution of these proteins by electronmicroscopy with specific ferritin-labelled antibodies; d) association constants of receptors for the proteins from different species; e) the nature of the carbohydrate containing receptors which we propose to isolate by affinity chromatography. 2. Embryonic chick brain. We have discovered a soluble agglutinin of formalinized erythrocytes from developing chick brain that is abundant early in chick brain development but not later. The agglutinin is a high molecular weight proteoglycan. We propose further characterization of this substance and its localization. We also propose to search for membrane bound agglutinins from embryonic chick brain fractions, including synaptosomes. In addition, we will examine possible heterogeneity of carbohydrate receptors on the surface of nerve terminals using a series of purified lectins.